Structure of PDB 4l7d Chain B Binding Site BS01

Receptor Information

>4l7d Chain B (length=285) Species: 9606 (Homo sapiens)

RLIYTAGGYFRQSLSYLEAYNPSDGTWLDLADLQVPRSGLAGCVVGGLLY
AVGGRNNSPDGNTDSSALDCYNPMTNQWSPCAPMSVPRNRIGVGVIDGHI
YAVGGSHGCIHHNSVERYEPERDEWHLVAPMLTRRIGVGVAVLNRLLYAV
GGFDGTNRLNSAECYYPERNEWRMITAMNTIRSGAGVCVLHNCIYAAGGY
DGQDQLNSVERYDVETETWTFVAPMKHRRSALGITVHQGRIYVLGGYDGH
TFLDSVECYDPDTDTWSEVTRMTSGRSGVGVAVTL

Ligand information

• Ligand ID: 1VX
• InChI: InChI=1S/C27H30N2O4/c1-17-7-6-12-21-19(17)13-14-29(26(31)22-10-4-5-11-23(22)27(32)33)24(21)16-28-15-18-8-2-3-9-20(18)25(28)30/h2-3,6-9,12,22-24H,4-5,10-11,13-16H2,1H3,(H,32,33)/t22-,23+,24-/m1/s1
• InChIKey: YTUXAQFRBNUADX-TZRRMPRUSA-N
• SMILES:
  CACTVS 3.385: Cc1cccc2[C@@H](CN3Cc4ccccc4C3=O)N(CCc12)C(=O)[C@@H]5CCCC[C@@H]5C(O)=O
  OpenEye OEToolkits 1.7.6: Cc1cccc2c1CCN(C2CN3Cc4ccccc4C3=O)C(=O)C5CCCCC5C(=O)O
  OpenEye OEToolkits 1.7.6: Cc1cccc2c1CCN([C@@H]2CN3Cc4ccccc4C3=O)C(=O)[C@@H]5CCCC[C@@H]5C(=O)O
  ACDLabs 12.01: O=C(O)C5CCCCC5C(=O)N2C(c1c(c(ccc1)C)CC2)CN4C(=O)c3ccccc3C4
  CACTVS 3.385: Cc1cccc2[CH](CN3Cc4ccccc4C3=O)N(CCc12)C(=O)[CH]5CCCC[CH]5C(O)=O
• Formula: C27 H30 N2 O4
• Name: (1S,2R)-2-{[(1S)-5-methyl-1-[(1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}cyclohexanecarboxylic acid
• ChEMBL: CHEMBL3890847
• ZINC: ZINC000098208041
• PDB chain: 4l7d Chain B Residue 701

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4l7d Binding Mode and Structure-Activity Relationships around Direct Inhibitors of the Nrf2-Keap1 Complex.
• Resolution: 2.25 Å
• Binding residue (original residue number in PDB): Y334 R380 N382 N414 R415 G509 A556 Y572 F577
• Binding residue (residue number reindexed from 1): Y9 R55 N57 N89 R90 G184 A231 Y247 F252
• Annotation score: 1
• Binding affinity: MOAD: ic50=0.75uM
  BindingDB: IC50=750nM

External links

• PDB: RCSB:4l7d, PDBe:4l7d, PDBj:4l7d
• PDBsum: 4l7d
• PubMed: 24504667
• UniProt: Q14145|KEAP1_HUMAN Kelch-like ECH-associated protein 1 (Gene Name=KEAP1)